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Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials

OBJECTIVE: This study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS). BACKGROUND: Previous post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phas...

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Autores principales: Ziemssen, Tjalf, Arnold, Douglas L., Alvarez, Enrique, Cross, Anne H., Willi, Roman, Li, Bingbing, Kukkaro, Petra, Kropshofer, Harald, Ramanathan, Krishnan, Merschhemke, Martin, Kieseier, Bernd, Su, Wendy, Häring, Dieter A., Hauser, Stephen L., Kappos, Ludwig, Kuhle, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009385/
https://www.ncbi.nlm.nih.gov/pubmed/35432382
http://dx.doi.org/10.3389/fimmu.2022.852563
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author Ziemssen, Tjalf
Arnold, Douglas L.
Alvarez, Enrique
Cross, Anne H.
Willi, Roman
Li, Bingbing
Kukkaro, Petra
Kropshofer, Harald
Ramanathan, Krishnan
Merschhemke, Martin
Kieseier, Bernd
Su, Wendy
Häring, Dieter A.
Hauser, Stephen L.
Kappos, Ludwig
Kuhle, Jens
author_facet Ziemssen, Tjalf
Arnold, Douglas L.
Alvarez, Enrique
Cross, Anne H.
Willi, Roman
Li, Bingbing
Kukkaro, Petra
Kropshofer, Harald
Ramanathan, Krishnan
Merschhemke, Martin
Kieseier, Bernd
Su, Wendy
Häring, Dieter A.
Hauser, Stephen L.
Kappos, Ludwig
Kuhle, Jens
author_sort Ziemssen, Tjalf
collection PubMed
description OBJECTIVE: This study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS). BACKGROUND: Previous post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phase 3 ASCLEPIOS I/II trials in which ofatumumab demonstrated better efficacy outcomes than teriflunomide, treatment with ofatumumab also led to significantly reduced sNfL levels compared to teriflunomide treatment. DESIGN/METHODS: In this study, we report protocol-planned analyses from the pooled ASCLEPIOS I/II trials (N=1882). Per protocol, patients were stratified by median baseline sNfL levels (9.3 pg/ml) into high (>median) and low (≤median) categories to prognosticate: annualized rate of new/enlarging T2 (neT2) lesions in year 1 and 2, annualized relapse rate, annual percentage change in whole brain (WB) and regional brain volume [thalamus, white matter (WM), cortical gray matter (cGM)], and disability outcomes. Similar analyses were performed for the recently diagnosed (within 3 years), treatment-naive patients (no prior disease-modifying therapy) subgroup. RESULTS: High versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p<0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, −0.32% vs. −0.24%, p=0.044, and teriflunomide, −0.43% vs. −0.29%, p=0.002), thalamic volume (−0.56% vs. −0.31%, p=0.047 and −0.94% vs. −0.49%, p<0.001), and WM volume (−0.30% vs. −0.19%, p=0.083 and −0.38% vs. −0.18%, p=0.003) but not of cGM volume (−0.39% vs. −0.32%, p=0.337 and −0.49% vs. −0.46%, p=0.563). A single sNfL assessment at baseline was not prognostic for on-study relapses or disability worsening. Results were similar in the subgroup of recently diagnosed, treatment-naive patients. CONCLUSION: This study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients.
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spelling pubmed-90093852022-04-15 Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials Ziemssen, Tjalf Arnold, Douglas L. Alvarez, Enrique Cross, Anne H. Willi, Roman Li, Bingbing Kukkaro, Petra Kropshofer, Harald Ramanathan, Krishnan Merschhemke, Martin Kieseier, Bernd Su, Wendy Häring, Dieter A. Hauser, Stephen L. Kappos, Ludwig Kuhle, Jens Front Immunol Immunology OBJECTIVE: This study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS). BACKGROUND: Previous post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phase 3 ASCLEPIOS I/II trials in which ofatumumab demonstrated better efficacy outcomes than teriflunomide, treatment with ofatumumab also led to significantly reduced sNfL levels compared to teriflunomide treatment. DESIGN/METHODS: In this study, we report protocol-planned analyses from the pooled ASCLEPIOS I/II trials (N=1882). Per protocol, patients were stratified by median baseline sNfL levels (9.3 pg/ml) into high (>median) and low (≤median) categories to prognosticate: annualized rate of new/enlarging T2 (neT2) lesions in year 1 and 2, annualized relapse rate, annual percentage change in whole brain (WB) and regional brain volume [thalamus, white matter (WM), cortical gray matter (cGM)], and disability outcomes. Similar analyses were performed for the recently diagnosed (within 3 years), treatment-naive patients (no prior disease-modifying therapy) subgroup. RESULTS: High versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p<0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, −0.32% vs. −0.24%, p=0.044, and teriflunomide, −0.43% vs. −0.29%, p=0.002), thalamic volume (−0.56% vs. −0.31%, p=0.047 and −0.94% vs. −0.49%, p<0.001), and WM volume (−0.30% vs. −0.19%, p=0.083 and −0.38% vs. −0.18%, p=0.003) but not of cGM volume (−0.39% vs. −0.32%, p=0.337 and −0.49% vs. −0.46%, p=0.563). A single sNfL assessment at baseline was not prognostic for on-study relapses or disability worsening. Results were similar in the subgroup of recently diagnosed, treatment-naive patients. CONCLUSION: This study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9009385/ /pubmed/35432382 http://dx.doi.org/10.3389/fimmu.2022.852563 Text en Copyright © 2022 Ziemssen, Arnold, Alvarez, Cross, Willi, Li, Kukkaro, Kropshofer, Ramanathan, Merschhemke, Kieseier, Su, Häring, Hauser, Kappos and Kuhle https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ziemssen, Tjalf
Arnold, Douglas L.
Alvarez, Enrique
Cross, Anne H.
Willi, Roman
Li, Bingbing
Kukkaro, Petra
Kropshofer, Harald
Ramanathan, Krishnan
Merschhemke, Martin
Kieseier, Bernd
Su, Wendy
Häring, Dieter A.
Hauser, Stephen L.
Kappos, Ludwig
Kuhle, Jens
Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
title Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
title_full Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
title_fullStr Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
title_full_unstemmed Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
title_short Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials
title_sort prognostic value of serum neurofilament light chain for disease activity and worsening in patients with relapsing multiple sclerosis: results from the phase 3 asclepios i and ii trials
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009385/
https://www.ncbi.nlm.nih.gov/pubmed/35432382
http://dx.doi.org/10.3389/fimmu.2022.852563
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